Infectious diseases are a major cause of morbidity and mortality and contribute substantially to health care costs in the United States. Infections account for approximately 30% of hospital admissions. In particular, septicemia, pneumonia, acute respiratory infections, cellulitis, and abscesses account for a substantial number of hospital admissions. Ranked fifth as an underlying cause of death in 1980, infectious diseases have risen to the third-ranked cause of death in the last several years, just behind cardiovascular disease and malignancies.
An estimated 26-53% of hospitalized patients receive at least one antibiotic. Kunin, C. M., “Problems in antibiotic usage,” in Mandell G. L. et al. Principles and practice of infectious diseases, 3rd ed., John Wiley & Sons, 427-34 (1989); Maki, D. G. and A. Schuna, “A study of antimicrobial misuse in a university hospital,” Am. J. Med. Sci., 275:271-82 (1978); and Bryan, C. S. et al., “Analysis of 1,186 episodes of gram-negative bacteremia in non-university hospitals: the effect of antimicrobial therapy,” Rev Infect Dis, 5:629-36 (1983). Timely and appropriate antibiotic administration improves survival in patients with serious infections. Pestotnik, S. L. et al., “Implementing antibiotic practice guidelines through computer-assisted decision support: clinical and financial outcomes,” Ann Intern Med., 124:884-90 (1996); Evans, R. S. et al., “Improving empiric antibiotic selection using computer decision support,” Arch Intern Med., 154:878-84 (1994).
Unfortunately, antimicrobial therapy for these patients is often inappropriate. Errors in dosing and selection of antimicrobial therapy are common. For example, it is estimated that 22-40% of antibiotic prescriptions are incorrect. Yu, V. L. et al., “Antimicrobial selection by computer,” JAMA, 242:1279-82 (1979); Dunagan, W. C. et al., “Antimicrobial misuse in patients with positive blood cultures,” Am J Med, 87:253-9 (1989); and Byl, B. et al., “Risk factors for inappropriate antimicrobial therapy of bacteremia, relation to the outcome,” in Program and abstracts of the 38th interscience conference on antimicrobial agents and chemotherapy,” Wash., D.C., American Society for Microbiology, (1998). Such inappropriate therapy is associated with increased patient mortality, adverse drug reactions, increased hospital costs, and emergence of multiple drug-resistant bacteria.
The major cause of inappropriate antibiotic therapy is the complexity of the prescribing process. There are more than 90 parental and oral antibiotics from which to choose. When prescribing antibiotics, clinicians must consider a bewildering array of data including an antibiotic's pharmacokinetic profile, relative efficacy, toxicities, local resistance patterns, drug-drug interactions, patient allergies, and drug costs. Other considerations are the site of infection, likely microorganisms present and their usual antimicrobial sensitivity patterns, patient alterations in renal, cardiac, and hepatic function; and the severity of the patient's illness. Therefore, it is difficult for clinicians who are not extensively trained in the administration of antimicrobial agents to make correct choices.
A number of approaches to solving the problem of suboptimal antibiotic therapy have been attempted, including formulary restriction, drug utilization review, rapid reporting of culture and susceptibility reports, computer-based decision support, and pharmacy intervention programs. Pestonik, S. L. et al., “Implementing antibiotic practice guidelines through computer-assisted decision support: clinical and financial outcomes,” Ann Intern Med., 124:884-90 (1996); Lesar T. S. and L. L. Briceland,” Survey of antibiotic control policies in university-affiliated teaching institutions,” Ann Pharmacother, 30:31-4 (1996); Rifenburg, R. P. et al., “Benchmark analysis of strategies hospitals use to control antimicrobial expenditures,” Am Health-Syst Pharm, 53(17):2054-62 (1996); Goldman, D. A. et al., “Strategies to prevent and control the emergence and spread of antimicrobial-resistant microorganisms in hospitals,” JAMA, 276:234-40 (1996); Quintiliani, R. et al., “Economic impact of streamlining antibiotic administration,” Am J Med, 82(suppl 4A):391-4 (1987); and Doem, G. V. et al., “Clinical impact of rapid in vitro susceptibility testing and bacterial identification,” J Clin Microbiol, 32:1757-62 (1994). Formulary changes within a drug class seldom produce meaningful differences in patient disease outcomes, and restrictive formularies achieve only modest cost savings by themselves. Drug utilization reviews seldom affect outcomes because they occur long after the prescribing event. Sophisticated computerized decision-support programs can be effective but are expensive and not available for general use. Rapid microbiology reports may result in savings but only partly address the problem of inappropriate antimicrobial therapy. In another large, prospective, observational study, it was reported that mortality was nearly halved when appropriate antibiotics were administered. Leibovici, L. et al., “Monotherapy versus β-lactam-aminoglycoside combination treatment for gram-negative bacteremia: a prospective, observational study,” Antimicrob Agents Chemother, 41:1127-33 (1997). It would follow that any system that would improve antibiotic selection would improve sepsis mortality.
In 1988, the Infectious Diseases Society of America (IDSA) developed guidelines for improving the use of antimicrobials in hospitals. The society suggested the creation of antimicrobial teams to improve antimicrobial use. See Marr, J. J. et al., “Guidelines for Improving the use of antimicrobial agents in hospitals: a statement by the Infectious Diseases Society of America,” J Infect Dis, 159-593-4 (1989). Prohibitive factors such as associated expenses, time, manpower, and equipment necessary to plan and implement such teams have prevented hospital administrators from further developing the teams to their potential.
Although systems to improve antibiotic use, such as those described above, have been applied in many hospitals all over the world, the vast majority of these systems have failed to substantially improve antimicrobial usage. The reasons for the failures are myriad. Even if these teams are funded and implemented, the difficulty remains in the timing of the delivery of information from these teams to the clinician at the actual time of antibiotic prescription. Generally speaking, these systems are heavy handed and slow, and are often antagonistic to the physician. In general, these teams have not achieved their potential results largely due to clinician resistance to pharmacy recommendations because they are often clinically irrelevant or delayed.
A randomized study performed at Alachua General Hospital in Gainesville, Fla. (see Gums, J. G., Yancey R. W. et al., “A Randomized, Prospective Study Measuring Outcomes after Antibiotic Therapy Intervention by a Multidisciplinary Consult Team,” Pharmacotherapy, 19(12):1369-1377 (1999)) demonstrated that optimizing antibiotic use results in more rapid patient discharge and improved survival. Furthermore, the study demonstrated that a high level of physician acceptance (86%) could be obtained if multidisciplinary team advice was carefully crafted and monitored to be clinically relevant and timely.
In this study, a team consisting of an infectious diseases specialist, a specially trained pharmacist, and the microbiology laboratory, was assembled to determine if the multidisciplinary team approach to antimicrobial usage would improve patient outcomes. Specifically, the team was assigned to address antimicrobial usage in a select patient population receiving suboptimal intravenous antibiotics after the initial prescription. The study results revealed that a team approach would be useful in reducing costs associated with intervention and length of stay on a case-by-case basis. There was no discussion, however, as to how to implement the team approach in the hospital as a whole, of using the team in the actual time of the antibiotic prescriptions, nor of using the comprehensive process to control resistant bacteria.